Hypophosphatemia and renal phosphate wasting are observed in oncogenic osteomalacia and the humoral hypercalcemia of malignancy. Two hypercalcemic rat models, the Leydig cell tumor and the Walker breast carcinosarcoma, also demonstrate hypophosphatemia and renal phosphate wasting. Some patients and animals bearing the Leydig cell and Walker tumors also have increased urinary cyclic AMP excretion. We have tested the Leydig-cell-tumor-culture-conditioned media for a direct effect to alter the renal handling of phosphate. Control cell culture media is infused into the left renal artery of fed, anesthetized, male Sprague-Dawley rats during equilibration and 20 min control clearance and then switched to Leydig-cell-tumor-exposed media, equilibrated and followed by two consecutive 20 min experimental clearances. Time-control experiments are also performed. With tumor-conditioned media, the fractional excretion of phosphate (FE(PO4)) increases from 1.2plus or minus 0.3% in the control clearance to 4.0 plus or minus 2.2 and 3.7 plus or minus 1.1% in the first and second experimental clearances respectively (p less than 0.05 from the control clearance for both). In time-control experiments, the FE(PO4) in the left kidney remains low, starting at 0.8 plus or minus 0.4% and not changing over three 20 min clearances. In these same experiments, we are unable to detect an alteration in urinary cyclic AMP excretion, in contrast to a significant increase in urinary cyclic AMP excretion when bovine PTH (1-84) is infused. Thyroparathyroidectomized, PO4-infused rats have been studied under a similar protocol. Tumor-conditioned media is associated with an increase in FE(PO4)) when basal FE(PO4)) ranges from 10 to 20%, but not when basal FE(PO4)) is greater than 35%. Infusion of Walker tumor-conditioned media was not associated with any change in the renal handling of PO4, thus preventing further study but also serving as an important negative control. (D)